Compound 1, tenofovir alafenamide (TAF or GS-7340) is one of the main ingredients in the FDA-approved anti-AIDS drug Genvoya. The drug was developed by Gilead. Tenofovir alafenamide is a nucleic acid reverse transcriptase inhibitor and a potential drug for tenofovir.
The formula of tenofovir alafenamide is C21H29N6O5P, which has a molecular weight of 467.5. The chemical structural formula of tenofovir alafenamide is as follows:

Chemical raw materials of active pharmaceutical ingredients (API) must have good purity, stability, physical and chemical properties and operability. These properties are related to the crystalline Form of the drug, and different crystal Forms have different physical and chemical properties. The purpose of improving the stability of the drug preservation and the efficacy of the drug, it is necessary to make the raw API into crystal Form.
A drug may exist in a plurality of crystalline Forms, and different crystal Forms of the same drug may have different dissolution and absorption in the body, thereby affecting the dissolution and release of the Formulation.
The optimal crystalline Form can be discovered by thoroughly studying of the polymorphism of the compound. The optimal crystalline Form is crucial to the efficacy of the drug and the Formulation process which is based on the characteristics of the crystalline Form, thereby effectively ensuring the equivalence of the drug batch to batch.
The physicochemical properties of the pharmaceutically active substance can be improved by selecting the form of its appropriate salt: such as solubility, dissolution rate, stability, purity, and the like. These physical and chemical properties further influence the quality and bioavailability of the drug. However, the choice of counter ion pairs used for salt formation and the formation of salts are not always straightforward, as the physical and chemical properties of different counter ions forming salts with the same compounds can vary widely. Some of salts can improve physical and chemical properties while some salt cannot be improved. Sometimes, the salt even has the poor physical and chemical properties. Therefore, finding and manufacturing a salt for pharmaceutically developable and improving the physical properties of a drug is a practical creation work.
A drug and a salt thereof may exist in a plurality of crystalline form states, and different crystal forms of the same drug and its salt may have different dissolution and absorption in the body, thereby affecting dissolution and release of the preparation.
The research on the polymorphic form of the drug and its salt can find the optimal crystalline form of the drug which is beneficial to the action of the drug, and at the same time, determine the formulation process according to the characteristics of the crystalline form, and effectively ensure the equivalence of the batch drug in the production.
Tenofovir alafenamide hemifumarate is one of the main components of the anti-AIDS drug Genvoya. The Genovya combination also contains other drugs such as Elvitegravir, cobicistat, emtricitabine. In the current technology, when TAF hemifumarate crystal form I (WO2013025788A1) is mixed with emtricitabine to form a tablet, the chemical stability of TAF is affected, and degradation products are easily generated, thereby affecting the quality and efficacy of the combination formulation. In order to solve this difficult problem, we have unexpectedly discovered that the new crystalline form II, monofumarate (form A) and sesquifumarate (form B) of TAF can significantly improve the chemical compatibility of TAF with emtricitabine, which makes this comb formulation more stable and improves quality and shelf life.